Faculty Bibliography

GOALS OF WORK: The goals of the study were to determine the occurrence rates for and the severity of symptoms at the middle, end, and 1 month after the completion of radiation therapy (RT), to determine the number and types of symptom clusters at these three time points, and to evaluate for changes over time in these symptom clusters. MATERIALS AND METHODS: Symptom occurrence and severity were evaluated using the Memorial Symptom Assessment Scale (MSAS) in a sample of patients (n = 160) who underwent RT for breast or prostate cancer. At each time point, an exploratory factor analysis was done to determine the number of symptom clusters (i.e., symptom factors) based on the MSAS symptom severity ratings. MAIN RESULTS: The majority of the patients were male and married with a mean age of 61.1 years. The five symptoms with the highest occurrence rates across all three time points were lack of energy, pain, difficulty sleeping, feeling drowsy, and sweats. Although the number of symptoms and the specific symptoms within each symptom cluster were not identical across the three time points, three relatively similar symptom clusters (i.e., "mood-cognitive" symptom cluster, "sickness-behavior" symptom cluster, "treatment-related", or "pain" symptom cluster) were identified in this sample. The internal consistency coefficients for the mood-cognitive symptom cluster and sickness-behavior symptom cluster were adequate at > or =0.68. CONCLUSIONS: Three relatively stable symptom clusters were found across RT. The majority of the symptom cluster severity scores were significantly higher in patients with breast cancer compared to patients with prostate cancer.

Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers.

The purpose of this article was to provide a comprehensive review of the epidemiological and genetic factors associated with ovarian cancer. A more complete understanding of the determinants of ovarian cancer may lead to the development of better screening and detection methods for this disease. The first section of this article reviews current literature on screening and early detection of ovarian cancer. The second section reviews the epidemiology of ovarian cancer, specifically highlighting the risk factors associated with the development of this disease. The article concludes with a discussion of how oncology nurses can apply this information to improve patient care.

OBJECTIVE: To evaluate for differences in subjective and objective measures of sleep between physically active and inactive female family caregivers of oncology patients at the initiation of their spouses' radiation therapy and evaluate for differences in demographic, clinical, and symptom characteristics between women in the 2 activity groups. DESIGN: Descriptive, cross-sectional study. SETTING: Two radiation treatment centers. PARTICIPANTS: Female family caregivers of patients who began radiation therapy for prostate, lung, or brain cancer. METHODS: Women were categorized as inactive (n=38) or active (n=30) based on self-report ratings of activity over a period of 2 days. Activity groups were compared on demographic and clinical characteristics, self-reported measures of sleep and other symptoms, and objective measures of sleep using wrist actigraphy. RESULTS: Inactive women had a higher number of comorbid conditions, lower levels of attentional function, less self-reported sleep time, a longer sleep onset latency, and a higher percentage of daytime sleep as measured by actigraphy compared with active women. CONCLUSIONS: Inactivity in female family caregivers of oncology patients is associated with poorer self-reported sleep and decreased attentional function.

OBJECTIVES: To investigate the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene as a potential modifier gene for coronary heart disease (CHD) in patients with familial hypercholesterolemia (FH). BACKGROUND: The ALOX5AP gene is required for the synthesis of leukotrienes, a protein family involved in inflammatory responses. Recently, genetic variation in this gene was shown to be associated with myocardial infarction in an Icelandic and British population. Since FH is characterized by severely increased levels of plasma low-density lipoprotein (LDL) cholesterol levels, chronic inflammation of the arterial wall, and subsequent premature CHD, the ALOX5AP gene could be an important modifier gene for CHD in FH. METHODS: In a cohort of 1817 FH patients, we reconstructed two four-marker haplotypes, previously defined in Icelandic (HapA) and British (HapB) individuals. The haplotypes were inferred with PHASE and the associations between the haplotypes and CHD were analyzed with a Cox proportional hazards model, adjusted for year of birth, sex, and smoking. RESULTS: HapB had a frequency of 6.9% and 8.2% in the group without and with CHD, respectively, conferring a hazard ratio of 1.48 (95% CI 1.17-1.89, p=0.001). This association was predominantly found in patients with LDL cholesterol levels above the median (HR 1.82, 95% CI 1.20-2.76, p=0.005). HapA was not associated with CHD. CONCLUSION: We conclude that genetic variation in the ALOX5AP gene contributes to CHD risk in patients with FH. Our findings emphasize the important role of inflammation in the pathogenesis of early CHD in this disorder, particularly in patients with more severely raised LDL cholesterol levels.

Findings from several studies suggest that oncology patients undergoing active treatment experience multiple symptoms, and that these symptoms can have a negative effect on patient outcomes. However, no systematic review has summarized the findings from studies that assessed multiple symptoms in these patients. Therefore, the purposes of this review were to: 1) compare and contrast the characteristics of the three most commonly used instruments to measure multiple symptoms; 2) summarize the prevalence rates for multiple symptoms in studies of oncology patients receiving active treatment; 3) describe the relationships among selected demographic, disease, and treatment characteristics and multiple symptoms; and 4) describe the relationships between the occurrence of multiple symptoms and patient outcomes (i.e., functional status, quality of life). Only 18 studies were found that met the inclusion criteria for this review. The majority of the studies were cross-sectional with sample sizes that ranged from 26 to 527. Approximately 40% of patients experienced more than one symptom. However, little is known about the relationships between demographic and clinical characteristics and the occurrence of multiple symptoms. Findings from this review suggest that the occurrence of multiple symptoms is associated with decreased functional status and quality of life. However, given the large number of oncology patients who undergo active treatment each year, additional research is warranted on the prevalence and impact of multiple symptoms. Only when this descriptive research is completed with homogenous samples of patients in terms of cancer diagnoses and treatments can intervention studies for multiple symptoms be developed and tested.

Predictors of and trajectories for evening and morning fatigue were evaluated in family caregivers of oncology patients using hierarchical linear modeling. Evening fatigue trajectory fit a quadratic model. Predictors included baseline sleep disturbances in family caregivers and baseline evening fatigue in patients. Morning fatigue trajectory fit a linear model. Predictors were baseline trait anxiety, levels of perceived family support, and baseline morning fatigue in patients. Findings suggest considerable inter-individual variability in the trajectories of evening and morning fatigue. Evaluating family caregivers for sleep disturbance, anxiety, and poor family support, as well as high levels of patient fatigue, could identify those family caregivers at highest risk for sustained fatigue trajectories.

OBJECTIVE: There is increasing physiological evidence in rodents connecting the neuropeptide galanin to triglyceride (TG) levels. We hypothesized that variation in the galanin preproprotein (GAL) gene may contribute to hypertriglyceridemia (HTG) in humans. METHODS AND RESULTS: We investigated GAL as a TG candidate gene by genotyping 4 tagSNPs in Dutch, Finnish, and Mexican familial combined hyperlipidemia (FCHL) families as well as in white combined hyperlipidemia cases/controls (n=2471). The common allele of rs2187331, residing in the promoter region of GAL, was significantly associated with HTG (probability value=0.00038). In an unascertained population sample of 4463 Finnish males, the rare allele of rs2187331 was associated with higher TGs (probability value=0.0028 to 0.00016). We also observed an allele specific difference with rs2187331 in reporter gene expression and nuclear factor binding in vitro. Furthermore, we detected differential expression of many key lipid genes in adipose tissue based on rs2187331 genotypes. CONCLUSIONS: The SNP rs2187331 is associated with HTG in FCHL and white combined hyperlipidemia cases/controls and influences TG levels in the population. Further studies are warranted to elucidate the allelic difference observed between FCHL and the general population. Functional evidence shows that rs2187331 has an allele specific cis-regulatory function and influences the expression of lipid related genes in adipose.

We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.